| 1. |
- Andreasen, Laura, et al.
(författare)
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Brugada syndrome-associated genetic loci are associated with J-point elevation and an increased risk of cardiac arrest
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:JUL
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, to increase the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed to investigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population. Materials and Methods: A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40-50] years, 49% males), with available digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.6-13.4] years. Data on outcomes were collected from Danish administrative healthcare registries. Furthermore, ~400,000 persons from UK Biobank were investigated for associations between the three loci and cardiac arrest/ventricular fibrillation (VF). Results: Homozygote carriers of the C allele in rs6800541 intronic to SCN10A had a significantly larger J-point elevation (JPE) compared with wildtype carriers (11 vs. 6 μV, P < 0.001). There was an additive effect of carrying multiple BrS-associated risk alleles with an increased JPE in lead V1. None of the BrS-associated genetic loci predisposed to syncope, atrial fibrillation, or total mortality in the general Danish population. The rs9388451 genetic locus adjacent to the HEY2 gene was associated with cardiac arrest/VF in an analysis using the UK Biobank study (odds ratio = 1.13 (95% confidence interval: 1.08-1.18), P = 0.006). Conclusions: BrS-associated risk alleles increase the JPE in lead V1 in an additive manner, but was not associated with increased mortality or syncope in the general population of Denmark. However, the HEY2 risk allele increased the risk of cardiac arrest/VF in the larger population study of UK Biobank indicating an important role of this common genetic locus.
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| 2. |
- Barauskas, Justas, et al.
(författare)
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Thermomyces lanuginosus lipase-catalyzed hydrolysis of the lipid cubic liquid crystalline nanoparticles
- 2016
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Ingår i: Colloids and Surfaces B. - : Elsevier. - 0927-7765 .- 1873-4367. ; 137, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- In this study well-ordered glycerol monooleate (GMO)-based cubic liquid crystalline nanoparticles (LCNPs) have been used as substrates for Thermomyces lanuginosus lipase in order to establish the relation between the catalytic activity, measured by pH-stat titration, and the change in morphology and nano-structure determined by cryogenic transmission electron microscopy and synchrotron small angle X-ray diffraction. The initial lipase catalyzed LCNP hydrolysis rate is approximately 25% higher for large 350 nm nanoparticles compared to the small 190 nm particles, which is attributed to the increased number of structural defects on the particle surface. At pH 8.0 and 8.4 bicontinuous Im3m cubic LCNPs transform into "sponge"-like assemblies and disordered multilamellar onion-like structures upon exposure to lipase. At pH 6.5 and 7.5 lipolysis induced phase transitions of the inner core of the particles, following the sequence Im3m cubic -> reversed hexagonal -> reversed micellar Fd3m cubic -> reversed micelles. These transitions to the liquid crystalline phases with higher negative curvature of the lipid/water interface were found to trigger protonation of the oleic acid produced during lipase catalyzed reaction. The increase curvature of the reversed discrete micellar cubic phase was suggested to cause an increase in the oleic acid pK(a) to a larger value observed by pH-stat titration. (C) 2015 Elsevier B.V. All rights reserved.
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| 3. |
- Stamm, Arne, et al.
(författare)
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The triolein/aqueous interface and lipase activity studied by spectroscopic ellipsometry and coarse grained simulations
- 2018
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Ingår i: Chemistry and Physics of Lipids. - : Elsevier BV. - 0009-3084 .- 1873-2941. ; 211, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- In spite of the importance of the triglyceride aqueous interface for processes like emulsification, surfactant interactions and lipase activity, relatively little is known about this interface compared to that between alkanes and water. Here, the contact between triolein and water was investigated in terms of water inclusion in the oil phase and orientation of the molecules at the interface. Coarse grained models of triglycerides in contact with water were constructed and correlated with experimental results of the changes in thickness and refractive index, obtained using spectroscopic ellipsometry of spin-coated triolein films. The topography of the layer was revealed by atomic force microscopy. Dry triolein and a triolein sample after equilibration with water were also compared structurally using small-angle X-ray scattering. Additionally, the kinetics of adsorption/activity of three different variants of the Thermomyces lanuginosus lipase (TLL) were investigated. The results show that uptake of water in the triolein phase leads to increase in thickness of the layer. The observed increase of thickness was further enhanced by an active lipase but reduced when an inactive mutant of the enzyme was applied.
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| 4. |
- Svendsen, Allan, et al.
(författare)
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Editorial
- 2018
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Ingår i: Chemistry and Physics of Lipids. - : Elsevier BV. - 0009-3084. ; 211, s. 1-3
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Tidskriftsartikel (refereegranskat)
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